The role of NMDA receptors in rat propofol self-administration

Abstract

Background: Propofol is among the most frequently used anesthetic agents, and it has the potential for abuse. The N-methyl-D-aspartate (NMDA) receptors are key mediators neural plasticity, neuronal development, addiction, and neurodegeneration. In the present study, we explored the role of these receptors in the context of rat propofol self-administration. Methods: Sprague-Dawley Rats were trained to self-administer propofol (1.7 mg/kg/infusion) using a fixed-ratio (FR) schedule over the course of 14 sessions (3 h/day). After training, rats were intraperitoneally administered the noncompetitive NDMA receptor antagonist MK-801, followed 10 min later by a propofol self-administration session. Results: After training, rats successfully underwent acquisition of propofol self-administration, as evidenced by a significant and stable rise in the number of active nose-pokes resulting in propofol administration relative to the number of control inactive nose-pokes (P < 0.01). As compared to control rats, rats that had been injected with 0.2 mg/kg MK-801 exhibited a significantly greater number of propofol infusions (F (3, 28) = 4.372, P < 0.01), whereas infusions were comparable in the groups administered 0.1 mg/kg and 0.4 mg/kg of this compound. In addition, MK-801 failed to alter the numbers of active (F (3, 28) = 1.353, P > 0.05) or inactive (F (3, 28) = 0.047, P > 0.05) responses in these study groups. Animals administered 0.4 mg/kg MK-801 exhibited significantly fewer infusions than animals administered 0.2 mg/kg MK-801 (P = 0.006, P < 0.01). In contrast, however, animals in the 0.4 mg/kg MK-801 group displayed a significant reduction in the number of active nose-poke responses (F (3, 20) = 20.8673, P < 0.01) and the number of sucrose pellets (F (3, 20) = 23.77, P < 0.01), while their locomotor activity was increased (F (3, 20) = 22.812, P < 0.01). Conclusion: These findings indicate that NMDA receptors may play a role in regulating rat self-administration of propofol.

NMDA receptor within nucleus accumbens shell regulates propofol self‐administration through D1R/ERK/CREB signalling pathway

“…Our behavioural findings align with a previous study demonstrating that systemic pretreatment of MK801 significantly enhances the number of propofol infusions in self-administration behaviour. 25 Despite the concentration of dopamine in the NAc was not detected in this study, previous research has found that intra-NAc infusions of AP5 and MK-801 can enhance DA release, and the attenuation of excitatory amino acid that induces activation of GABA input to DA neurons in the VTA is thought to be the underlying mechanisms. [34][35][36] Besides, in vivo brain microdialysis studies show that propofol increases dopamine level in the NAc in rats in subanaesthetic and anaesthetic doses.…”

“…Previous research has demonstrated that NMDAR‐D1R/ERK/CREB signal transduction pathway is critical in the regulation of reward‐seeking behaviour 20 . It has been suggested that NMDARs may be involved in regulating propofol self‐administration 25 . The results indicate that intraperitoneally administered MK801, a non‐competitive channel blocker of NMDARs, facilitates propofol self‐administration behaviour in rats 25 .…”

“…25 The results indicate that intraperitoneally administered MK801, a non-competitive channel blocker of NMDARs, facilitates propofol self-administration behaviour in rats. 25 However, the underlying mechanisms have not been explored. By far, it remains unknown whether the NMDAR-D1R/ERK/CREB signal transduction pathway in the NAc regulates propofol self-administration.…”

“…It has been suggested that NMDARs may be involved in regulating propofol self‐administration 25 . The results indicate that intraperitoneally administered MK801, a non‐competitive channel blocker of NMDARs, facilitates propofol self‐administration behaviour in rats 25 . However, the underlying mechanisms have not been explored.…”

Hippocampal blood–brain barrier of methamphetamine self‐administering HIV‐1 transgenic rats

“…Rats were trained to self-administer meth in operant chambers equipped with two "nose-poke" holes, a stimulus light above each hole, an audio tone generator and a house light. Nosepoking is an ethologically relevant behavior and a commonly employed operant task with rodents (e.g., Brown et al, 2020;Chen et al, 2020;Fredriksson et al, 2019;Gordon-Fennell et al, 2019;Hong, Kang, Chen, & Choi, 2019;Oliva & Wanat, 2019). Each operant chamber was enclosed in a ventilated, sound-attenuating chamber.…”